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Acquired TERT promoter mutations stimulate TERT transcription in mantle cell lymphoma
Author(s) -
Panero Julieta,
AlvesPaiva Raquel M.,
Roisman Alejandro,
SantanaLemos Barbara A.,
Falcão Roberto P.,
Oliveira Gustavo,
Martins Diego,
Stanganelli Carmen,
Slavutsky Irma,
Calado Rodrigo T.
Publication year - 2016
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.24324
Subject(s) - mantle cell lymphoma , telomerase , biology , cancer research , lymphoma , telomere , somatic cell , mutation , microbiology and biotechnology , telomerase reverse transcriptase , gene , genetics , immunology
Mantle cell lymphoma (MCL) is an aggressive lymphoid neoplasm with poor prognosis. Acquired telomerase reverse transcriptase gene promoter ( TERT p) mutations are among the most frequent somatic non‐coding mutations in cancers. In this study, the prevalence of TERT p mutations in 24 MCL and 21 other lymphoid neoplasias (oLN) was investigated. Eight MCL samples (33%) carried TERT p mutations, two homozygous and six heterozygous (seven C228T and one C250T), which directly correlated with higher TERT transcription, mitochondrial DNA copy number, and IGHV mutational status in MCL neoplastic cells. TERT p mutations were not found in oLN. TERT p mutations correlated with more lymphoma proliferation and tumor burden, as suggested by the higher number of lymphoma cells circulating in peripheral blood, and tended to associate with longer MCL telomeres, especially in homozygous mutants, although not statistically significant. Telomere‐biology genes were overexpressed in MCL cells in comparison to healthy lymphocytes, but were not influenced by mutation status. The findings described for the first time that acquired TERT p mutations are common in MCL but not in other lymphoid neoplasms. It was also demonstrated that TERT p mutations are associated with higher TERT mRNA expression in MCL cells in vivo and higher tumor burden, suggesting these mutations as a driver event in MCL development and progression. Am. J. Hematol. 91:481–485, 2016. © 2016 Wiley Periodicals, Inc.